Maternal C3 complement and C-reactive protein and pregnancy and fetal outcomes: A secondary analysis of the PEARS RCT-An mHealth-supported, lifestyle intervention among pregnant women with overweight and obesity.

OBJECTIVES: Elevated circulating levels of complement component 3 (C3) and C-reactive protein (CRP) have been linked with adverse pregnancy outcomes. Lifestyle interventions may hold potential to ameliorate these effects. We investigated the effect of an antenatal healthy lifestyle intervention on maternal C3 and CRP concentrations and assessed their relationship with maternal and fetal metabolic markers and outcomes. STUDY DESIGN: Secondary analysis of data from the Pregnancy Exercise And Nutrition Research Study (PEARS) randomized controlled trial. METHODS: Women (n = 406) with C3 and CRP concentrations determined in early pregnancy (14-16 weeks) and/or late pregnancy (28-weeks) with corresponding fasting glucose, insulin, c-peptide, and lipid profiles were included in the analysis. Pregnancy outcomes included: diagnoses of gestational diabetes (GDM), pre-eclampsia (PET) or pregnancy induced hypertension (PIH), pre-term birth (delivery < 37 weeks), low birth weight (<2500 g), small-for-gestational age (SGA) defined using < 5th or 10th centile for birthweight and cord blood measures of glucose and lipid metabolism. T-tests investigated changes in C3 and CRP over time. Chi-square, Pearson's' correlations and multiple regression investigated relationships with outcomes. RESULTS: The PEARS intervention did not influence maternal C3 or CRP concentrations in pregnancy. There was no relationship between CRP concentrations and any maternal or infant outcome. Women who developed GDM had higher C3 concentrations in early (p = 0.01) and late pregnancy (p = 0.02). Women who developed PIH/PET had lower C3 concentrations in early (p = 0.02), but not late (p = 0.10) pregnancy. Maternal C3 concentrations in early pregnancy were a small but significant predictor of maternal insulin concentrations in early (ß = 0.40, 95% CI 0.27, 0.53; p < 0.001) and late (ß = 0.30, 95% CI 0.17, 0.43p < 0.001) pregnancy, early total cholesterol (TC), and both early and late triglycerides, LDL and HDL Cholesterol concentrations (all p < 0.001). Women who delivered SGA babies (<10th centile) had lower C3 concentrations than women who did not in both early (p < 0.001) and late pregnancy (p = 0.01). No relationship between maternal C3 or CRP and fetal glucose concentrations or lipid profiles was observed. CONCLUSION: Maternal C3 may play a role in multiple adverse pregnancy outcomes including cardiometabolic ill-health. Further research on this, and strategies to reduce C3 in a pregnant population, are warranted.

An mHealth-Supported antenatal lifestyle intervention may be associated with improved maternal sleep in pregnancy: Secondary analysis from the PEARS trial.

OBJECTIVE: To investigate the effect of an antenatal diet and exercise intervention during pregnancy on sleep duration. As a secondary objective, associations between sleep duration and gestational weight gain (GWG), maternal metabolic parameters and pregnancy outcomes were assessed. DESIGN: Secondary analysis. SETTING: Large tertiary Maternity Hospital in Dublin, Ireland. POPULATION: 326 women with overweight or obesity who participated in the Pregnancy Exercise And Nutrition Research Study (PEARS) randomised controlled trial between March 2013 and August 2016. METHODS: Secondary analysis of a randomised trial. MAIN OUTCOME MEASURES: Impact of the PEARS intervention on sleep duration, and association of sleep duration and maternal metabolic parameters, and pregnancy outcomes. RESULTS: Participants had a mean age of 32.5 ± 4.5 years and median (interquartile range [IQR]) body mass index of 28.3 (26.6-31.2) kg/m2 . The intervention group had a longer sleep duration in late pregnancy (mean difference 17.1 minutes (95% confidence interval [CI] 0.5-33.7) and a higher proportion achieving optimum sleep duration of 7-9 h (54.3 vs. 42.9%, relative risk [RR] 1.28 (95% CI 1.01-1.62). In late pregnancy, sleep duration of <6 h was associated with lower breastfeeding rates on discharge (RR 0.74, 95% CI 0.57-0.95) and higher triglyceride levels (mean difference 0.24, 95% CI 0.10-0.38). There were no significant associations between sleep and incidence of gestational diabetes mellitus or pre-eclampsia/toxaemia, or other metabolic parameters assessed (insulin, fasting glucose, HOMA-IR). CONCLUSION: A diet and exercise intervention from early pregnancy may promote longer and optimal sleep duration, with maternal benefits such as lower triglyceride levels and higher breastfeeding rates.

Gestational weight gain in obese pregnancy: impact on maternal and foetal metabolic parameters and birthweight.

The aim of this prospective, observational study was to investigate the impact of gestational weight gain (GWG) among euglycaemic obese pregnant women on maternal and foetal metabolic parameters and neonatal outcome. Total GWG was recorded for 101 obese, non-diabetic women with a singleton pregnancy. At 28 weeks of gestation, fasting maternal blood samples were analysed for glucose, insulin, c-peptide and lipids. Cord bloods were collected at delivery for analysis of glucose, c-peptide and lipids. GWG (mean ± SD =10.9 ± 5.5 kg) was greatest among those of younger age and lower body mass index and 58% of women exceeded the Institute of Medicine GWG recommendations of 5-9 kg for obese pregnancy. GWG was significantly positively associated with increased risk of birthweight >4 kg, cord c-peptide levels and inversely associated with cord total cholesterol. This study identified that higher GWG in obese pregnancy may increase the risk of macrosomia and neonatal hyperinsulinaemia, within a euglycaemic maternal cohort. Impact statement Excess gestational weight gain (GWG) and maternal obesity frequently co-occur with adverse consequences for maternal and neonatal health; however, little is known of the underlying biological pathways which may be affected to contribute to adverse outcomes. Greater understanding of the biological mechanisms involved may help guide future studies to develop targeted interventions for more effective clinical outcomes. This study identified that higher GWG among obese pregnant women resulted in foetal hyperinsulinaemia even in the absence of maternal hyperglycaemia, potentially representing a biological pathway for larger birthweight babies. These results may highlight the need for more intensive dietary and lifestyle interventions among obese women who would not normally receive additional counselling beyond standard antenatal care if not diagnosed with glucose intolerance in pregnancy.

Behaviour change in overweight and obese pregnancy: a decision tree to support the development of antenatal lifestyle interventions.

OBJECTIVE: Antenatal healthy lifestyle interventions are frequently implemented in overweight and obese pregnancy, yet there is inconsistent reporting of the behaviour-change methods and behavioural outcomes. This limits our understanding of how and why such interventions were successful or not. DESIGN: The current paper discusses the application of behaviour-change theories and techniques within complex lifestyle interventions in overweight and obese pregnancy. The authors propose a decision tree to help guide researchers through intervention design, implementation and evaluation. The implications for adopting behaviour-change theories and techniques, and using appropriate guidance when constructing and evaluating interventions in research and clinical practice are also discussed. CONCLUSIONS: To enhance the evidence base for successful behaviour-change interventions during pregnancy, adoption of behaviour-change theories and techniques, and use of published guidelines when designing lifestyle interventions are necessary. The proposed decision tree may be a useful guide for researchers working to develop effective behaviour-change interventions in clinical settings. This guide directs researchers towards key literature sources that will be important in each stage of study development.

The Interplay between Maternal Nutrition and Stress during Pregnancy: Issues and Considerations.

BACKGROUND: Several studies about humans and animals have separately examined the effects of prenatal nutrition and stress on fetal development, pregnancy, and birth outcomes, and subsequent child health and disease risk. Although substantial evidence from non-pregnant literature supports the presence of bidirectional interactions between nutrition and stress at various psychological, behavioral, and physiological levels, such interaction effects have not yet been systematically examined in the context of pregnancy. SUMMARY: This paper discusses the multifaceted and multilevel relationship between nutrition and stress. It then reviews the currently available observational and experimental evidence in animals and humans regarding the interplay between maternal psychosocial stress, dietary intake, and nutritional state during pregnancy, and implications for maternal and child health-related outcomes. Key Messages: During pregnancy, maternal psychosocial stress, dietary behavior, and nutritional state likely regulate and counter-regulate one another. Emerging evidence suggests that omega-3 fatty acids may attenuate maternal psychosocial stress, and that high maternal pre-pregnancy body mass index exacerbates unhealthy dietary behaviors under high-stress conditions. Longitudinal studies are warranted in order to understand the interplay between prenatal psychosocial stress, diet, and stress- and nutrition-related biomarkers to obtain further insight and inform the development and design of future, more effective intervention trials for improved maternal and child health outcomes.

The association between childcare and risk of childhood overweight and obesity in children aged 5 years and under: a systematic review.

UNLABELLED: The aim of this paper was to systematically review the published evidence on the relationship between the type of childcare and risk of childhood overweight or obesity. The databases PubMed, MEDLINE, Cochrane Library and EMBASE were searched using combinations of the various search terms to identify eligible observational studies published between 2000 and May 2016 in English. Fifteen publications from 7 countries matched the inclusion criteria. The most commonly reported childcare arrangements were centre-based (e.g. crèche) and informal care (e.g. relatives, neighbours, friends). Informal care was most frequently associated with an increased risk of childhood overweight and obesity. Associations were also found for other lifestyle variables such as low maternal education, high birth-weight, maternal employment, ethnicity, maternal overweight/obesity and father's Body Mass Index (BMI). CONCLUSION: The relationship between childcare and childhood overweight/obesity is multi-faceted with many aspects linked to childhood adiposity, in particular the age of initiation to care, type of care (i.e. informal care) and shorter breastfeeding duration were related with infant adiposity. WHAT IS KNOWN: • Lifestyle factors during early years affect health outcomes in adulthood, particularly in children with low birth weight. • Pre-school stage influences children's body composition and growth. What is new: • This is the first systematic review of observational studies examining the association between childcare and childhood overweight and obesity in preschool children. • 'Informal' care is linked to early introduction to solid foods, less physical activity and obesity.

Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.

BACKGROUND: Interferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir. METHODS: We enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:1:2:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0-F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3-F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790. FINDINGS: 168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81-96] in cohort 1 and n=82 [94%, 87-98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3-4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12. INTERPRETATION: Combined simeprevir and sofosbuvir was efficacious and well tolerated. FUNDING: Janssen.

Impact of probiotics in women with gestational diabetes mellitus on metabolic health: a randomized controlled trial.

OBJECTIVE: Probiotics are live microorganisms that may confer health benefits on the host. Recent trials of probiotic use among healthy pregnant women demonstrate potential for improved glycemic control. The aim of this study was to investigate the effects of a probiotic capsule intervention on maternal metabolic parameters and pregnancy outcome among women with gestational diabetes. STUDY DESIGN: This double-blind placebo-controlled randomized trial recruited pregnant women with a new diagnosis of gestational diabetes or impaired glucose tolerance following a 3-hour 100-g glucose tolerance test. Women were randomized to a daily probiotic (Lactobacillus salivarius UCC118) or placebo capsule from diagnosis until delivery. Fasting blood samples were collected at baseline and 4-6 weeks after capsule commencement for analysis of glucose, insulin, c-peptide, and lipids. The primary outcome was difference in fasting glucose postintervention, first analyzed on an intention-to-treat basis and followed by per-protocol analysis that excluded women commenced on pharmacological therapy (insulin or metformin). Secondary outcomes were changes in insulin, c-peptide, homeostasis model assessment and lipids, requirement for pharmacological therapy, and neonatal anthropometry. RESULTS: Of 149 women recruited and randomized, there were no differences between the probiotic and placebo groups in postintervention fasting glucose (4.65 ± 0.49 vs 4.65 ± 0.53 mmol/L; P = 373), requirement for pharmacological therapy (17% vs 14%; P = .643), or birthweight (3.57 ± 0.64 vs 3.60 ± 0.57 kg; P = .845). Among 100 women managed with diet and exercise alone, fasting plasma glucose decreased significantly within both the probiotic (4.76 ± 0.45 to 4.57 ± 0.42 mmol/L; P < .001) and placebo (4.85 ± 0.58 to 4.58 ± 0.45 mmol/L; P < .001) groups, but the levels between groups did not differ (P = .316). The late gestation-related rise in total and low-density lipoprotein (LDL) cholesterol was attenuated in the probiotic vs the placebo group (+0.27 ± 0.48 vs +0.50 ± 0.52 mmol/L total cholesterol, P = .031; +0.08 ± 0.51 vs +0.31 ± 0.45 mmol/L LDL cholesterol, P = .011). No differences were noted between groups in other metabolic parameters or pregnancy outcome. CONCLUSION: A probiotic capsule intervention among women with abnormal glucose tolerance had no impact on glycemic control. The observed attenuation of the normal pregnancy-induced rise in total and LDL cholesterol following probiotic treatment requires further investigation, particularly in this obstetric group at risk of future metabolic syndrome.

Fetal metabolic influences of neonatal anthropometry and adiposity.

BACKGROUND: Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring. METHODS: Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity. RESULTS: Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant. CONCLUSION: Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

Lifestyle and dietary habits of an obese pregnant cohort.

Obese pregnant women are the focus of numerous dietary and lifestyle intervention studies, however there is a paucity of literature examining the habitual dietary and lifestyle habits of this population. This paper aims to assess maternal dietary and lifestyle habits in an obese cohort, in order to identify priority areas to be addressed in future studies and in clinical practice. This prospective observational study recruited 100 pregnant women with a body mass index 30.0-39.9 kg/m(2) from routine antenatal clinics. Dietary intakes were assessed using a 3-day food diary and a structured lifestyle questionnaire assessed physical activity levels, smoking and alcohol habits and wellbeing. Macronutrient intakes as a percentage of total energy were not compliant to healthy eating guidelines with an inadequate intake of carbohydrate and excess intake of saturated fat. Compliance to recommended intakes of calcium, iron, folate and vitamin D was poor from diet alone. The consumption of energy dense food groups high in fat and sugar was greater than for published pregnant populations and the general female non-pregnant population. One-third of women reported engaging in weekly physical activity that would comply with recommendations for pregnant women while 25 % reported low mood status indicating potential depression. High intakes of energy-dense processed foods and poor compliance to micronutrient recommendations are critical dietary issues of concern among obese pregnant women. Low mood is a barrier to motivation for changing behaviour which would also need to be addressed in future lifestyle intervention studies.

Development of a Culinary Medicine Curriculum to Support Nutrition Knowledge for Gastroenterology Fellows and Faculty.

Gastroenterologists encounter many nutrition-related disorders in their practice, yet the nutritional needs of patients with chronic gastrointestinal (GI) and liver disease are largely unaddressed by treating physicians, due to suboptimal nutrition education. To address this gap, we developed and piloted a culinary medicine course for a GI fellowship training program. The objective of this study is to describe the development, implementation, and acceptability of the course. A registered dietitian, a chef instructor, and a gastroenterology clinical professor trained in culinary medicine developed the four-class tailored curriculum and delivered the classes remotely. Each class had a theme related to commonly encountered GI disorders and included hands-on meal preparation, a nutrition lecture, and a patient case study discussion. Post-course feedback surveys were disseminated. Twenty-three GI physicians enrolled in the course and the attendance rates in classes 1-4 were 83%, 65%, 61%, and 48%, respectively. Among 15 completed feedback surveys, 80% reported that the class contents were either moderately or extremely useful and all endorsed the curriculum for other gastroenterologists. Future studies of culinary medicine programs tailored to medical specialties should identify strategies to maintain engagement and assess the impact on nutrition knowledge, competencies, and translation of these new skills to clinical practice.

Maternal Diet Quality and Prenatal Depressive Symptoms: The Moderating Role of Economic Well-Being.

Prenatal depression is prevalent and adversely impacts maternal and infant health. This study addresses a critical literature gap and investigates the association between maternal diet quality and prenatal depressive symptoms, as well as the moderating effect of economic well-being on this link. A cross-sectional design was used, including 43 healthy pregnant women in the second trimester aggregated from two research projects. Prenatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Dietary quality was evaluated using two non-consecutive 24 h dietary recalls, from which the Adapted Dietary Inflammatory Index (ADII) and the Healthy Eating Index (HEI)-2015 were derived. Economic well-being was indicated by the income-to-poverty ratio. A higher HEI-2015 (adherence to dietary guidelines; ß = -0.53, p = 0.01) and negative ADII (anti-inflammatory diet; ß = 0.40, p = 0.06) were associated with fewer prenatal depressive symp-toms. Among pregnant women with worse economic well-being, a pro-inflammatory diet was as-sociated with more prenatal depressive symptoms (b = 1.69, p = 0.004), but among those with better economic well-being, the association was not significant (b = 0.51, p = 0.09). Dietary interventions aimed at reducing dietary inflammation might hold some promise for improving mental health among pregnant women who are economically vulnerable.

Feasibility and Acceptability of a Mindfulness-Based Smartphone App among Pregnant Women with Obesity.

Maternal obesity is associated with an increased risk for prenatal depressive symptoms. Mindfulness-based interventions (MBIs) have been shown to reduce the risk of prenatal depression. This pilot study assesses the feasibility and acceptability of a smartphone-based MBI among pregnant women with obesity, and its potential for improving maternal mental and behavioral health outcomes. Five second-trimester pregnant women with a prepregnancy body mass index > 30 kg/m2 participated in a 30-day audio-guided mindfulness practice using the Headspace app. All participants engaged in the pregnancy module, while three concurrently engaged in the mindful eating module. Daily engagement with the app was tracked and a post-trial survey assessed maternal acceptability. Validated pre- and post-trial questionnaires explored changes in perceived stress, anxiety, depression, and eating habits. All participants completed the study with varying levels of adherence to the prescribed daily practice; the average number of days of engagement was 23/30 (77%) for the pregnancy module and 20/30 (67%) for the mindful eating module. All subjects reported some degree of perceived benefit, and none reported negative experiences. Trends were observed for improvements in maternal mental wellbeing and eating behaviors. This pilot study shows that a smartphone-based MBI is feasible, acceptable, and perceived to provide benefit among pregnant women with obesity.

Systematic Review of Easy-to-Learn Behavioral Interventions for Dietary Changes Among Young Adults.

INTRODUCTION: Improving the diet quality of young adults may support chronic disease prevention. The approaches used and efficacy of promoting small dietary behavior changes through easy-to-learn (ETL) interventions (requiring no more than 1 hour to teach the behavior) among young adults have not yet been systematically reviewed. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 2 independent electronic searches across 6 databases were conducted to identify any articles describing ETL interventions among young adults (aged 18-35 years) and reporting dietary intake outcomes. RESULTS: Among 9,538 articles identified, 9 studies met eligibility criteria. Five studies reported significant improvement in the selected dietary outcome. Of these, 3 studies used an implementation intentions approach, in which participants were given or asked to write out a simple dietary behavior directive and carry it on their person. Less than half of included studies were rated as positive for overall quality. DISCUSSION: The available evidence suggests that ETL interventions targeting the dietary behaviors of young adults may be effective in improving dietary intake. Limitations of included studies were lack of follow-up after the intervention period and low generalizability. IMPLICATIONS FOR RESEARCH AND PRACTICE: Further dietary intervention studies targeting young adults should systematically evaluate the efficacy of ETL intervention approaches among diverse samples.

Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C.

BACKGROUND & AIMS: High-level coffee consumption has been associated with reduced progression of pre-existing liver diseases and lower risk of hepatocellular carcinoma. However, its relationship with therapy for hepatitis C virus infection has not been evaluated. METHODS: Patients (n=885) from the lead-in phase of the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial recorded coffee intake before retreatment with peginterferon α-2a (180 µg/wk) and ribavirin (1000-1200 mg/day). We assessed patients for early virologic response (2 log10 reduction in level of hepatitis C virus RNA at week 12; n=466), and undetectable hepatitis C virus RNA at weeks 20 (n=320), 48 (end of treatment, n=284), and 72 (sustained virologic response; n=157). RESULTS: Median log10 drop from baseline to week 20 was 2.0 (interquartile range [IQR], 0.6-3.9) among nondrinkers and 4.0 (IQR, 2.1-4.7) among patients that drank 3 or more cups/day of coffee (P trend<.0001). After adjustment for age, race/ethnicity, sex, alcohol, cirrhosis, ratio of aspartate aminotransferase to alanine aminotransferase, the IL28B polymorphism rs12979860, dose reduction of peginterferon, and other covariates, odds ratios for drinking 3 or more cups/day vs nondrinking were 2.0 (95% confidence interval [CI]: 1.1-3.6; P trend=.004) for early virologic response, 2.1 (95% CI: 1.1-3.9; P trend=.005) for week 20 virologic response, 2.4 (95% CI: 1.3-4.6; P trend=.001) for end of treatment, and 1.8 (95% CI: 0.8-3.9; P trend=.034) for sustained virologic response. CONCLUSIONS: High-level consumption of coffee (more than 3 cups per day) is an independent predictor of improved virologic response to peginterferon plus ribavirin in patients with hepatitis C.

Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C.

BACKGROUND & AIMS: Interferon reportedly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial showed that 4 years of maintenance therapy with pegylated interferon (peginterferon) does not reduce liver disease progression. We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period. METHODS: The study included 1048 patients with chronic hepatitis C (Ishak fibrosis scores ≥ 3) who did not have a sustained virologic response (SVR) to therapy. They were randomly assigned to groups given a half-dose of peginterferon or no treatment (controls) for 3.5 years and followed up for a median of 6.1 (maximum, 8.7) years. RESULTS: Eighty-eight patients developed HCC (68 definite, 20 presumed): 37 of 515 who were given peginterferon (7.2%) and 51 of 533 controls (9.6%; P = .24). There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis, but not fibrosis, based on analysis of baseline biopsy samples. After 7 years, the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8% and 24.2%, respectively (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24-0.83); in treated and control patients with fibrosis, incidences were 8.3% and 6.8%, respectively (HR, 1.44; 95% CI, 0.77-2.69). Treated patients with a ≥ 2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs 9.4%; P = .03). CONCLUSIONS: Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs. Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls.

Reduction in Hepatic Inflammation Is Associated With Less Fibrosis Progression and Fewer Clinical Outcomes in Advanced Hepatitis C.

OBJECTIVES: During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. METHODS: Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological change was defined as a ≥ 2-point difference in HAI or Ishak fibrosis score between biopsies. RESULTS: Among 657 patients who received full-dose peginterferon/ribavirin "lead-in" therapy before randomization, year-1.5 HAI improvement was associated with lead-in HCV RNA suppression in both the randomized treated (P<0.0001) and control (P=0.0001) groups, even in the presence of recurrent viremia. This relationship persisted at year 3.5 in both the treated (P=0.001) and control (P=0.01) groups. Among 834 patients followed for a median of 6 years, fewer clinical outcomes occurred in patients with improved HAI at year 1.5 compared with those without such improvement in both the treated (P=0.03) and control (P=0.05) groups. Among patients with Ishak 3-4 fibrosis at baseline, those with improved HAI at year 1.5 had less fibrosis progression at year 1.5 in both the treated (P=0.0003) and control (P=0.02) groups. CONCLUSIONS: Reduced hepatic inflammation (measured 1.5 and 3.5 years after randomization) was associated with profound virological suppression during lead-in treatment with full-dose peginterferon/ribavirin and with decreased fibrosis progression and clinical outcomes, independent of randomized treatment.

A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C.

UNLABELLED: The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P<0.0001). Child-Turcotte-Pugh (CTP) score≥7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score≥7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis. CONCLUSION: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7.

Prenatal stress assessment using heart rate variability and salivary cortisol: A machine learning-based approach.

OBJECTIVE: To develop a machine learning algorithm utilizing heart rate variability (HRV) and salivary cortisol to detect the presence of acute stress among pregnant women that may be applied to future clinical research. METHODS: ECG signals and salivary cortisol were analyzed from 29 pregnant women as part of a crossover study involving a standardized acute psychological stress exposure and a control non-stress condition. A filter-based features selection method was used to identify the importance of different features [heart rate (HR), time- and frequency-domain HRV parameters and salivary cortisol] for stress assessment and reduce the computational complexity. Five machine learning algorithms were implemented to assess the presence of stress with and without salivary cortisol values. RESULTS: On graphical visualization, an obvious difference in heart rate (HR), HRV parameters and cortisol were evident among 17 participants between the two visits, which helped the stress assessment model to distinguish between stress and non-stress exposures with greater accuracy. Eight participants did not display a clear difference in HR and HRV parameters but displayed a large increase in cortisol following stress compared to the non-stress conditions. The remaining four participants did not demonstrate an obvious difference in any feature. Six out of nine features emerged from the feature selection method: cortisol, three time-domain HRV parameters, and two frequency-domain parameters. Cortisol was the strongest contributing feature, increasing the assessment accuracy by 10.3% on average across all five classifiers. The highest assessment accuracy achieved was 92.3%, and the highest average assessment accuracy was 76.5%. CONCLUSION: Salivary cortisol contributed a significant increase in accuracy of the assessment model compared to using a range of HRV parameters alone. Our machine learning model demonstrates acceptable accuracy in detection of acute stress among pregnant women when combining salivary cortisol with HR and HRV parameters.

Relationship between psychological stress and ghrelin concentrations in pregnant women with overweight or obesity.

Exposure to, perception of, and response to stress have all been shown to influence appetite and dietary behaviors in non-pregnancy human and animal studies, mediated in part by the appetite stimulating hormone ghrelin. Yet, the impact of prenatal stress on biological pathways associated with appetite in the context of pregnancy is not well understood. The objective of this study was to assess the relationship between these layered dimensions of stress with fasting and postprandial plasma ghrelin concentrations among Hispanic pregnant women with overweight or obesity, a population known to experience heightened levels of stress. Thirty-three non-diabetic Hispanic women with pre-pregnancy body mass index of 25.0-34.9 kg/m2 participated in a crossover study at 28-32 weeks' gestation. At each visit, participants provided fasting blood and saliva samples, consumed a standardized mixed-meal, and completed a 15-minute task: friendly conversation (control) or the Trier Social Stress Test (experimental stress exposure). Six timed blood and saliva samples were collected up to 2 h from baseline and assayed for ghrelin and cortisol, respectively, and area-under-the-curve (AUC) values were computed. Day-to-day stress levels were assessed by the Perceived Stress Scale. Physiological and psychological stress reactivity was determined by cortisol AUC and change in self-reported affect state, respectively, during the experimental stress visit. Maternal perceived stress was positively associated with ghrelin concentrations in the fasted (ß = 0.06, p = 0.02) and postprandial state (ß = 0.05, p = 0.02). Mean ghrelin AUC was not significantly different following acute stress versus control. Measures of acute stress reactivity were not associated with ghrelin AUC. Contrary to our hypothesis, among Hispanic pregnant women with overweight and obesity, exposure to an acute stress induction task did not alter postprandial ghrelin concentrations, and changes in individual psychological and physiological stress reactivity did not associate with postprandial ghrelin. However, our findings suggest that maternal report of general perceived stress over the last month is associated with higher fasting and postprandial ghrelin concentrations. Differences in the effects of short-term stress exposure versus day-to-day perception of stress on appetite and food intake in pregnancy deserves further investigation.